Clotting cascade initiating apparatus and methods of use and methods of closing wounds

ABSTRACT

Wound closure methods and apparatus are provided which utilize blood fluid by activating the clotting cascade of the blood fluid outside the body within a substantially enclosed sterile container then introducing the blood fluid to the wound site to complete clotting. Methods and apparatus for providing ways of inhibiting anticoagulants and slowing fibrin clot degradation are also disclosed. Kits for practicing the invention singularly or in combination with and/or associated with preferred procedures are also disclosed.

BACKGROUND OF THE INVENTION

[0001] 1. Field of Invention

[0002] This invention concerns novel methods and apparatus for medicalapplications, specifically wound closure applications. Moreparticularly, the invention manipulates blood fluids, or its components,in new ways to close tissue or vascular wounds.

[0003] 2. Background Information

[0004] Numerous medical applications exist where sealing of biologicaltissue is desired. U.S. Pat. No. 5,510,102 to Cochrum identifies many ofthese including trauma of liver, spleen, pancreas, lung, bone, etc.,cardiovascular and vascular, such as microvascular anastomoses, vasculargrafts, intraoperative bleeding, and aortic repair, for thoracic surgerysuch as lung biopsy, for transplant of heart, renal, pancreas, lung,bone or bone marrow, for neurosurgery such as nerve anastomoses, or CSFleak repair, for endoscopic surgery, such as hemostasis in hepatictrauma, or bile duct repair, for interventional radiology, such ashemostasis for percutaneous liver biopsy or vascular occlusion, forgastrointestinal surgery such as colonic anastomoses, for obstetrics andgynecology such as rectovaginal fistulas, for pediatric and fetalsurgery, for plastic surgery and burn repairs such as grafting processof cultured epidermis, for dermatology such as hair transplants, fordental surgery, for ophthalmic cataract surgery, for urology, forcorrection of urinary fistulas and such others. With such broadapplication of the present invention possible, one use is selected formethod and apparatus illustrative continuity purposes throughout thisdocument. The selected application is sealing of a vascular woundresulting from percutaneous entry as is frequently done in theperformance of angiography, angioplasty, and atherectomy procedures.

[0005] Percutaneous vascular access is typically done in the context ofperforming some minimally invasive surgical procedure. Minimallyinvasive techniques are used to reduce trauma to the patient. Reducedtrauma typically translates to improved patient comfort, less proceduralcomplications, and lower costs. The vessel accessed is typically thefemoral or radial artery. Access involves placement of an introducer'sdistal tip beneath the patient's skin and through the arterial wall. Tothe extent possible, percutaneous access preserves the integrity oftissue covering the artery. As a result, when the introducer is to beremoved the arterial access site is not exposed and the arterial woundis preferably closed without cutting down through the overlaying tissueto expose the site.

[0006] To accomplish hemostasis at the wound, numerous methods ofpost-introducer arterial closure have been invented. Most of these aresimilar to each other in many respects with some novel differentiatingcharacteristic separating them. All of them rely upon the clottingcascades being initiated at the wound site. All prior art devices may bebroadly classified into two groups—those that passively support on setof the clotting cascades at the wound site and those that actively causethe clotting cascades at the wound site. By example, mechanical methodsof holding the wound closed by clamping or suturing to preventhemorrhaging are passive methods because they merely prevent continualflushing of the site as the clot attempts to take hold. To a lesserdegree the body also does this naturally by vascular constriction. Thesecond grouping—active clotting at the wound site—includes those methodswhich place a clot inducing material at the wound site. Such clotinducing formulations are many and typically either supply thrombindirectly or stimulate thrombin release at the wound site.

[0007] Disadvantages of the prior art vary based on the method employed.Generally speaking, passive devices like clamping or suturing are eithercomplex or expensive. Clamping for example can be labor intensive toadminister manually and is uncomfortable for the patient by any meansSuturing on the other hand is complex and expensive because the woundsite is typically small, remote, and blind to the physician placing thesuture. Active devices are often costly and potentially dangerous.Active devices typically require placement of a clot-inducing foreignmaterial in the patient which necessitates either expensive pretestingfor potential allergic reactions or accepting the occasional adversereaction which could lead to anaphylactic shock and even death asreported in J. Trauma, 31:408 (1991). Transmission of infectiousdiseases can occur when the material used was manufactured from pooledhuman blood as reported in Opth. Surg., 23:640 (1992). Autologouspreparations like fibrin glue as described in U.S. Pat. No. 5,674,394 toWhitmore are well known but significant preparation with the associatedlabor and material costs are required and typically an additionalthrombin material must still be added at the wound site.

[0008] Despite the need for a device and method which overcomes thelimitations of the prior art, none insofar as is known has been proposedor developed until the present invention.

[0009] Accordingly, it will be appreciated that there is a need for anefficient way of closing wounds. The present inventions provideadvantages over the prior devices and the prior methods used to closewounds, and also offers other advantages over the prior art and solvesother problems associated therewith.

SUMMARY OF THE INVENTION

[0010] This present invention provides methods of closing a woundincluding the steps of treating a blood fluid such that the clottingcascade is initiated and transporting the treated blood fluid to thewound to form a clot at the wound thereby preventing fluid from passingthrough the wound. The invention further provides the clotting cascadeinitiation apparatus including a clotting cascade initiation apparatuswithin which a blood fluid can be received, the blood fluid being usefulfor treatment of a wound within a patient, said apparatus including asubstantially enclosed sterile containment chamber within which theblood fluid can be received and retained, and a procoagulating agentwithin the substantially enclosed sterile containment chamber wherein aclotting cascade can be initiated when the blood fluid is accepted in tothe sterile containment chamber and exposed to the wound within thepatient subsequent to the initiation of the clotting cascade such thatthe clotting cascade can be completed and a clot can form within thewound. The invention further provides the method of using the clottingcascade initiation apparatus including the steps of providing a means tosubstantially neutralize an anticoagulant. The invention furtherprovides the method of using the clotting cascade initiation apparatusincluding the steps of providing a means to substantially neutralize ananticlot. The invention further provides the method of using theclotting cascade initiation apparatus including providing a kit toconveniently practice the method.

[0011] It is believed that the present invention offers significantadvantages over the prior art methods and apparatuses. By activating theblood fluid clotting cascade within a substantially enclosed sterilecontainer outside the patient prior to placement at the wound site, amyriad of clot performance enhancing possibilities are allowed whichwould otherwise be difficult or barred from practice if they had to beperformed in the patient's body at the wound site. With such an expandedcapability to manipulate the blood fluid, it is believed dramaticimprovements may be realized in clot formation control, efficacy,reliability, safety, cost performance; anticoagulant inhibition control,efficacy, reliability, safety, cost performance; anticlot inhibitioncontrol, efficacy, reliability, safety, cost performance; and generalapparatus ergonomic user friendliness, efficacy, reliability, safety,cost performance, and the like, should be attainable.

[0012] These and various other advantages and features of novelty thatcharacterize the present invention are pointed out with particularity inthe claims annexed hereto informing a part hereof However, for a betterunderstanding of the present invention, its advantages and other objectsobtained by its use, reference should be made to the drawings, whichform a further part hereof and to the accompanying descriptive matter,in which there is illustrated and described preferred embodiments of thepresent invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013] The invention will be further described in connection with theaccompanying drawings, in which:

[0014]FIG. 1 is a mosaic pictorial of example apparatus components,

[0015]FIG. 2 is a pictorial view of the two principal apparatuscomponent assemblies used for illustration.

[0016]FIG. 3 is a pictorial of the assembled apparatus example as it ispositioned initially in a patient; and

[0017]FIG. 4 is a pictorial of a method and apparatus example aspositioned for return of blood fluid.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0018] As used herein, the following terms have the following meanings:“Blood fluid” means a fluid containing natural components of wholeblood, whether derived from whole blood, whole blood extracts, orproducts of ex vivo cell cultures, the blood fluid containing sufficientblood components to enable a portion of the blood fluid to clotsubsequent to the initiation of a clotting cascade; “Clottingcascade(s)” means those chemical reactions occurring in blood whichresult in clot formation; “Clot” means a solidified mass of blood fluidhaving at least 90% of the available fibrin polymer crosslinked;“Biocompatible” means an agent is regarded by the regulating governmentbody to be acceptable for implant in the human body; “Procoagulant”means a component capable of causing the blood fluid to form clot;“Anticoagulant” means a component capable of preventing blood fluid clotformation; “Homogenous clot activation” means the blood fluid volumebegins to form clot at substantially the same time and rate throughoutits volume; and “Anticlot inhibitor” means any of the naturallyoccurring blood fluid components which play a role in dissolution offibrin clot. All patents, patent applications, and references citedherewithin are hereby incorporated by reference.

[0019] The current invention concerns a novel method and apparatus foruse in hemostatic closure of tissue wounds. The invention activates theclotting cascade of the blood fluid then transports the treated bloodfluid to the wound in the patient such that the blood fluid can comeinto contact with the patient proximate the wound such that a clot isformed in the wound which prevents fluid from passing through the wound.The invention provides the opportunity to manipulate the blood fluid inrespects needed to achieve the desired clot formation in the wound. Thistypically includes the elements of basic clot formation, including butnot limited to, converting fibrinogen to a fibrin monomer then fibrinpolymer which ultimately becomes a cross-linked fibrin polymer; controlof anticoagulants including, but not limited to, coumarin drugs,aspirin, Integrilin, Reapro, or a streptokinase enzyme; and ultimatelycontrol of dissolution of the fibrin clot involving, but not limited to,serine proteases. By containing blood fluid to be used in wound clotformation and activating the clotting cascade under controlled sterileconditions outside the patient, the present invention method andapparatus provides the opportunity to manipulate the blood fluid used toform wound clot in many ways not before possible.

[0020] An apparatus to be used for sterile enclosed containment of theblood fluid may exist in many forms. A representative example of suchenclosures would include syringes, cartridges, vials, test tubes, jars,bags, balloons, pouches, trays, dishes, bowls, tubing, catheters,cannula in general, and the like. A common feature to such containerswould include the ability to keep the container substantially enclosedthereby preventing a level of contamination or loss of sterilityunacceptable to the user. In practice, one or more containers may usedseparately or in combination. For example, a syringe connected to acatheter may be regarded as two containers or a single container with atransfer means, depending on the context of the discussion it is usedin. Both context are acceptable and not intended to be limiting.Likewise, a single container may have one or more chambers internal toit. As a result, a single container with multiple chambers may bereferred to as a single container or multiple containers. A gain, bothreferrals are acceptable and should be interpreted in the context of thediscussion and not be interpreted as to be limiting.

[0021] Generally, the containers have at least one fluid communicationelement associated with it which connects the inside to the outside ofthe container. A fluid communication element may have a normally openhole such as a luer fitting, a normally closed hole such as a septum, ora selective opening such as a molecular sieve or semipermeable membrane,and the like.

[0022] Procoagulant refers to any element causing the blood fluid toform clot. Procoagulants may be any such acting material, combination ofmaterials, or mechanical activity. Mechanical proagulants include bloodfluid agitation, thermal induction, lysis, and the like. Procoagulantmaterials include those of biological origin such as cotton, thrombin,and the like. Procoagulant further includes inorganic materials likeglass and the like. Procoagulant additionally includes synthetic organicmaterials like aminocaproic acid and the like, or polymers like dacron,nylon, polypropylene, silicone, and the like. Procoagulants may be usedsingularly or in combination.

[0023] Procoagulants, as with anticoagulant inhibitors and anticlotinhibitors discussed further on, may exist as an integral function ofsome other component, a coating on some other component, or be containedin some other component. Using procoagulants for illustrative purposes,an integral function example would be a glass walled container and thelike. Glass causes the blood fluid to start clot formation while it alsoserves the functions of maintaining containment and sterility of theblood fluid. A coating example would be a static mixer having a surfacebonded with diatomaceous earth and the like. An example of procoagulantcontainment in some other component may be either the presence of cottonloose within a container, the holding of thrombin in at least onechamber of multiple chambers in a container, or a container withinanother container, such as an inner sealed breakable vial containingaminocaproic acid, an inner container made from porous microbeadsinfused with aminocaproic acid, and the like.

[0024] Procoagulants, anticoagulant inhibitors, anticlot inhibitors andthe like, may be added at the time of use, either before, during, orafter and either singularly, sequentially, or in any combination witheach other or with the blood fluid. Depending on the phase state of thematerial—gaseous, liquid, or solid, those skilled in the art can combineknown hardware elements to implement the transfer.

[0025] As a preferred embodiment, the combining of procoagulant,anticoagulant inhibitor, anticlot inhibitor, and the like, eitherbefore, during, or after and either singularly, sequentially, or in anycombination with blood fluid, preferably should be accomplished forhomogenous respective functional results throughout the blood fluid. Byexample, a glass walled container can combine the functions ofprocoagulant, containment, and maintenance of sterility, however, unlessthe container is small, such as with a bundle of capillary-like tubeswithin a larger container, homogenous activation of the clotting cascadewithin the blood fluid does not occur. Specifically, a glass wallenclosing an undesirable large space would rapidly activate the clottingcascade of only that blood fluid close to the glass wall. Blood fluid ata distance from the wall reacts slower or not at all. The less thandesirable result is that blood fluid at the glass wall forms a boundarylayer of mature clot—that having substantial cross-linked fibrinpolymer—which typically has little use because its adhesive capabilityand structure are often disrupted and destroyed during transport to thewound site. Likewise, the other zones of the blood fluid withoutclotting cascade activation do not clot in the wound site as desired.This clotting mechanism may be used but the aforementioned inferiorresults are to be expected, hence it is a preferred embodiment toprovide ways to improve homogeneity of the desired blood fluid reaction.Apparatus examples accomplishing this include a static mixer, dynamicmixer, a porous matrix, and the like. Examples of a porous matrixinclude glass beads or cotton in a container—both provide a high surfacearea for intimate contact and turbulence within the blood fluid as itpasses through the matrix. Thus, it may otherwise be stated that flowingblood fluid is preferred over pooled static blood and turbulent flow ispreferred over laminar flow.

[0026] With regard to procoagulant, anticoagulant inhibitor, anticlotinhibitor and like materials, they may constitute more than onefunction, such as also making a static mixer, and the like, or they beseparate as discussed above. This brings forth other embodiments andadvantages of the invention. Specifically, it is also possible toclassify procoagulant, anticoagulant inhibitor, anticlot inhibitor, andthe like agents collectively as either catalytic or non-catalyticmaterials. By example, cotton is a catalytic material in the contextthat blood fluid is combined with it to initiate a reaction(procoagulation) in the blood fluid then it is separated, trace cottonfiber notwithstanding, and substantially retained from the blood fluidprior to returning the blood fluid to the wound site. To the contrary,the liquid drug protamine sulfate may be added to the blood fluid as anoncatalytic material, for example via an injection port septum on theenclosed sterile container, to initiate a reaction (inhibit theanticoagulant heparin) and stay with the blood fluid when it is returnedto the wound site. By further example, diethylaminoethyl cellulose(DEAE), a catalytic material, may be held inside of a container viafiltration methods and the like. When heparin anticoagulated blood fluidis added to the container, DEAE cellulose binds with the heparinremoving it from the blood fluid thus keeping both the heparin anditself from returning to the wound site, trace presence remaining inblood fluid notwithstanding. In the interest of avoiding adverse patientoutcomes, like an allergic response, it is a preferred embodiment of thepresent invention to not leave significant foreign materials in theblood fluid that is being returned to the wound site. As such, a benefitof the present invention is that by manipulating blood fluid to initiatethe clotting cascade outside the patient, it is possible to use manymore agents in catalytic form for procoagulation, anticoagulationinhibition, anticlot inhibition, and the like, than would be allowed ifthe selection was limited to agents that had to be biocompatible, e.g.,approved for implant in the body. This increased selection allows forreduction or elimination of compromises in product efficacy,reliability, and safety. Further, even when working with non-catalyticimplantable agents, the invention has new benefits such as the abilityto ensure appropriate blood fluid mixing, concentration, clot volume andthe like when performed outside the body.

[0027] Anticoagulant inhibitor is used to prevent any clot inhibitingagents present in the blood fluid from performing their function. Ananticoagulant inhibitor may be specific or General in function. Byexample, thrombin acts as a procoagulant but can serve double duty as ananticoagulant inhibitor simply by being present in volumes large enoughto overwhelm the volume of anticoagulant present in the blood fluid.With the exception of protein deficiencies associated with hemophilia,anticoagulation typically occurs as the result of adding a foreign agentto the blood. Such agents typically include coumarin drugs, aspirin,Integrilin, Reapro, or a streptokinase enzyme. In catalytic form,polymers of selective electrical charge, diethylaminoethyl cellulose,and the like, may be placed in the blood fluid, singularly or incombination with an anticoagulant inhibiting drug and the like, toattract and hold an anticoagulant. In the non-catalytic form, protaminesulfate and the like may be used to render inactive a drug like heparin.Examples and the preferred manner and form of introduction have beendiscussed above.

[0028] Anticlot inhibitor is a term used to describe anything thatimpairs the function of fibrin clot degradation. Degradation of fibrinclots is naturally a function of plasmin, a serine protease thatcirculates as the inactive proenzyme, plasminogen. Anticlot inhibitorsthus may serve in one way to disrupt the function of plasmin,plasminogen, and the like. Anticlot inhibitors may have value inextending the life of a wound sealing clot if desired. Examples of suchinhibitors would be tranexamic acids plasminogen binding material (PBM)available from Bioforma Research & Consulting, Inc., and the like. Theymay be applied in substantially the same way as discussed foranticoagulant inhibitors and procoagulants. Examples of the preferredmanner and form of introduction have been discussed above.

[0029] The preferred embodiments of the apparatus of the presentinvention may be highly varied and is typically dependent on theindividual application considering clinical situation, physicianpreference, and the like. As such, a clinical situation is selected andphysician preference stated here for purposes of providing anillustrative example of one form of the invention apparatus.Presentation of this scenario is intended to be an instructive exampleof how the invention may be adapted to individual needs and should notbe interpreted in a limited context as to how the invention applies.When used as a references those skilled in the art will be able to alterconfigurations and attributes of the apparatus to the same and otherneeds without departing from the scope and spirit of the presentinvention. The present example selected is that of post-introducerarterial wound closure following an angiographic procedure and the like.Post-introducer arterial wound closure typically involves the closure ofa wound within a arterial wall such as the femoral artery, radialartery, and the like. Such wounds are typically subcutaneous in thesense that the artery is covered by tissue rather than being exposed bycut down through the tissue until the artery is visible to thepractitioner. In the present illustration, an apparatus in configuredfor use typically with autologous whole blood.

[0030]FIG. 1 shows a typical array of components required to practicethe invention when used to hemostatically close a post-introducerarterial wound. An advantage of the present invention apparatus exampleis that the components used are with rare exception standardoff-the-shelf components commonly used throughout the medical industryand recognizable to those skilled in the art. A polymer 12 cc syrine 1consisting of a plunger rod 2 connected to a fluid sealing piston 4 isslidingly placed within a cylinder 3 thereby allowing the cylinder toreceive and expel fluids and the like through the distal port 5 of thesyringe 1. A three-way connector 6 permits fluid communication betweenits three ports. A three-way valve connector 7 permits selective fluidcommunication between its three ports. Luer lock cylinder cap fittings 8and 10, typically made of polycarbonate, are used to form a containerwhen assembled to the ends of cylinder 9, also typically mad ofpolycarbonate. Tubing section 11 represents a short section ofsubstantially clear tubing typically made from the polymer polypropyleneand the like. A porous material 12 typically made from cotton, open cellpolyurethane, and the like will be used as a component in thefabrication of a bacteria resistant air vent. The porous materials of 13and 15 represent both filtration and procoagulant materials and aretypically both made of cotton and the like and typically resemble acotton-ball consistency. Item 14 represents the anticoagulant bindingmaterial diethylaminoethyl (DEAE) cellulose. Item 16 represents theconstruct of a simple pulsitile indicator consisting of a substantiallyclear tube typically made of a polymer and having one end open 17 andthe opposing end 18 closed either by addition of a plug or a melting andthe like of the tube material. Tube 19 represents a length of tubingmade of polyethylene and the like which will be used as a catheter. Theouter diameter of tube 19 is typically the same french size as thatspecified for the introducer with which it is intended to be used Thedistal end 20 is closed to fluid flow and forms an atraumatic tip forplacement in an artery. The port 21 is proximal to the distal end 20 bytypically 4 cm and typically approximates two-thirds the inner diameterof the tube and is placed through one wall of the tube 19 therebypermitting fluid communication between the outside of the tube with theinside of the tube extending fully to the proximal end 20 of tube 19.Item 23 represents a mating connector for assembly to and use with theproximal end 20 of tube 19 and at least one open port of the three-wayconnector 6. Item 24 represents a snap collar intended to be slidinglyplaced over tube 19 and bonded to the outside of tube 19 along itslength between port 21 and proximal end 22. The contour of the snap fitof collar 24 is configured to connect with any one of several differentbrands of manufacture of introducer, an example of which is illustratedin FIG. 3.

[0031]FIG. 2 represents a typical assembly of the subcomponents in FIG.1 into a blood fluid processor 25 and a blood fluid transfer catheter29. The assembly 25 represents the three-way connector 6 attached toopen end of the pulsitile indicator 16 and distal end of the assembly ofeither cylinder cap fittings 8 or 10 from FIG. 1 as fitted to thecylinder 9 of FIG. 1 therein containing distally the cotton material 13,medially the diethylaminoethyl cellulose material 14, and proximally thecotton material 15. The function of the cotton material 13 is primarilythat of a filter which is used to retain the loose fibrousdiethylaminoethyl (DEAE) cellulose material 14. The DEAE cellulosematerial serves to bind with and retain the anticoagulant, heparin, inthe blood fluid to be used. The function of the cotton material 15 is toserve as a filter to retain the DEAE cellulose and also as aprocoagulant of the blood fluid. Item 30 represents the construct of abacteria resistant air vent. Item 12 from FIG. 1 placed in the distalend of tube 11 from FIG. 1. The proximal end of item 30 is attached toone port of the three-way valve 7 of FIG. 1 which in-turn mates thesyringe port 5 of FIG. 1 with the proximal end cap connector 8 of FIG. 1which is part of the aforementioned assembly containing the cotton andDEAE. The item of 29 represents the completed catheter assemblydiscussed above.

[0032]FIG. 3 represents the completed apparatus assembly in-place withinthe introducer and patient as it would typically be used. Catheter 29 isshown placed through the introducer 32 with proximal end 33 snap fittedto the catheter and extending beyond the distal end 34 until port 21 isin fluid communication with the inside of artery 36 which issubstantially enclosed within living tissue 35. Accordingly, blood fluidflows through port 21 up through catheter 29 and into the pulsitileindicator 16 and the containing apparatus assembly 31. The arterialsystolic/diastolic pressure variation causes blood fluid within thepulsitile indicator 16 to vary compression of the entrapped air spacewithin 16 thus providing positive indication of the presence of port 21within the artery. The three-way valve of 31 is turned to permitwithdrawal of the syringe plunger thereby encouraging blood fluid toflow through the cotton and DEAE cellulose. As this occurs trapped airwithin the syringe may be exhausted by switching the three valve to theexhaust side and advancing the plunger. Once substantially exhausted ofair, the three-way valve is returned to the position which permits bloodfluid to enter the syringe upon withdrawal of the plunger. As bloodfluid flows through the apparatus toward the accumulating syringe, DEAEbinds with and removes heparin from the blood fluid and the cottonpresent causes activation of the clotting cascade within the blood fluidas it passes through the cotton on its way to the accumulating syringe.

[0033]FIG. 4 represents the placement of blood fluid having an activatedclotting cascade at the wound site. Both the catheter and introducer arewithdrawn from the patient until there is a cessation of movement withinthe blood fluid 39 within the pulsitile indicator thus indicating thatthe catheter's distal port is now outside the artery. Once this has beenestablished, the syringe plunger is advanced thereby drivingclot-activated blood fluid 40 out the distal catheter port anddepositing it about the wound where clotting continues. As the bloodfluid 40 continues to advance to a mature clot, proximal pressure isapplied to the artery and both the introducer and catheter are fullyremoved from the patient. After typically 3 to 5 minutes, proximaldirect pressure may be eliminated and the procedure considered complete.Although not presented in this example, anticlot inhibition may havealso been used if desired as previously discussed. Those skilled in theart will observe that blood fluid between the distal catheter port andthe DEAE cellulose material escaped removal of anticoagulant.Experimentation has shown that such residual anticoagulant does notinhibit clot formation in the considerable larger volume of activatedblood fluid. However, if this were a problem, it certainly would bepossible to have a closed loop apparatus so that blood fluid does nottravel the same fluid communication conduit to and from the wound area.Alternatively, an anticoagulant inhibitor may be placed within thecatheter starting at the distal port and extend all the way back throughto the proximal end of the device if desired These alternatives merelyillustrate examples of the tremendous latitude available to a productdesigner within the present invention.

[0034] In providing the user with a functional construct of the presentinvention, it may be desirable to provide the user with a kit ofcomponents bundled together for ease of use. As with other aspects ofthe invention illustrated earlier, this invention aspect can take manyforms and is typically dependent on clinical application, userpreferences, and the like. As such, the following is merely anillustrative example of what a kit may consist of and should not beinterpreted as a limitation of the present invention. For the sake ofcontinuity with previous illustrations, this illustration will be in thecontext of a typical kit for use with minimally invasive angiographicprocedures and the like. Thus, the kit may contain a wound closureapparatus of the present invention singularly or in combination with oneor more of the following: an introducer, guidewire, dilator, obturator,collapsible catheter sheath, Seldinger needle, balloon catheter,infusion catheter, stent, scalpel, suture line, needle, pouch, tray,tray lid, instructions for use, adhesive identification label, sterilityindicator, and the like.

[0035] It is to be understood, however, that even though numerouscharacteristics and advantages of the present invention have been setforth in the foregoing description, together with details of thestructure and function of present invention, the sequence or order ofthe specific steps, or the actual compositions or materials used mayvary somewhat. Furthermore, it will be appreciated that this disclosureis illustrative only and that changes may be made in detail, especiallyin matters of shape, size, arrangement of parts or sequence or elementsof aspects of the invention within the principles of the invention tothe full extent indicated by the broad general meaning of the terms inwhich the appended claims, which form a further part hereof, areexpressed.

What is claimed is:
 1. A method of closing a wound in a patient, themethod comprising the steps of: a) treating a blood fluid such that atleast a portion of the blood fluid will form a clot of blood subsequentto the treatment, the blood fluid containing sufficient blood componentsto enable a portion of the blood fluid to clot subsequent to thetreatment once a clotting cascade is initiated, the blood componentsbeing select from the group consisting of whole blood, naturalcomponents of whole blood, whether derived from whole blood, bloodextracts, or products of ex-vivo cell cultures, and procoagulatingagents which assist in or enhance the clotting or coagulation of theblood fluid, the step of treating the blood fluid including initiatingthe clotting cascade; and b) transporting the treated blood fluid to thewound in the patient such that the blood fluid can come into contactwith the patient proximate the wound and the clotting cascade can comegenerally to a conclusion and a clot can form proximate the wound suchthat a clot is formed in the wound which prevents fluid from passingthrough the wound.
 2. The method of claim 1; the step of treating theblood fluid including (1) providing a containment chamber in which theblood fluid can be contained; (2) placing the blood fluid in thecontainment chamber; and (3) initiating the clotting cascade by exposingthe blood fluid to a procoagulating agent within the containmentchamber.
 3. The method of claim 2, the step of treating the blood fluidincluding providing a substantially enclosed sterile containmentchamber, the chamber containing a procoagulating agent.
 4. The method ofclaim 3, wherein the procoagulating agent is a porous matrix and thestep of treating the blood fluid includes passing the blood fluidthrough the porous matrix.
 5. The method of claim 4, wherein the porousmatrix is biological in origin and the step of treating the blood fluidincludes exposing the blood fluid to the biologic material such that theclotting cascade is initiated within the blood fluid.
 6. The method ofclaim 5, wherein the biologic material is a biologic agent is cotton,diatomaceous earth.
 7. The method of claim 4, wherein the porous matrixis an inorganic material and the step of treating the blood fluidincludes exposing the blood fluid to the inorganic material such thatthe clotting cascade is initiated within the blood fluid.
 8. The methodof claim 7, wherein the inorganic material is glass.
 9. The method ofclaim 4, wherein the porous matrix is a synthetic polymer and the stepof treating the blood fluid includes exposing the blood fluid to thesynthetic polymer such that the clotting cascade is initiated within theblood fluid.
 10. The method of claim 9, wherein the synthetic polymeragent is a synthetic polymer selected from the group consisting ofdacron, silicone, polyurethane, polycarbonate, polyethylene,polyvinylchloride.
 11. A clotting cascade initiation apparatus withinwhich a blood fluid can be received, the blood fluid being useful fortreatment of a wound within a patient, said apparatus comprising: asubstantially enclosed sterile containment chamber within which theblood fluid can be received and retained; and a procoagulating agentwithin the substantially enclosed sterile containment chamber; wherein aclotting cascade can be initiated when the blood fluid is accepted intothe sterile containment chamber and exposed to the procoagulating agent,and the blood fluid can be delivered to the wound within the patientsubsequent to the initiation of the clotting cascade such that theclotting cascade can be completed within the wound and a clot can formwithin the wound.
 12. The clotting cascade initiation apparatus of claim11, further including a cannula for delivering blood fluid to the wound,the cannula being in communication with the containment chamber.
 13. Theclotting cascade initiation apparatus of claim 11, further including acannula for withdrawing blood fluid from the patient and deliveringblood fluid to the wound, the cannula being in communication with thecontainment chamber.
 14. The clotting cascade initiation apparatus ofclaim 11, wherein the procoagulating agent is a porous matrix throughwhich the blood fluid can be passed.
 15. The clotting cascade initiationapparatus of claim 14, wherein the porous matrix is biological inorigin.
 16. The clotting cascade initiation apparatus of claim 15,wherein the biologic material is a biologic material selected from thegroup consisting of cotton, diatomaceous earth.
 17. The clotting cascadeinitiation apparatus of claim 14, wherein the porous matrix is aninorganic material.
 18. The clotting cascade initiation apparatus ofclaim 17, wherein the inorganic material is glass.
 19. The clottingcascade initiation apparatus of claim 14, wherein the porous matrix is asynthetic polymer.
 20. The clotting cascade initiation apparatus ofclaim 19, wherein the synthetic polymer is a synthetic polymer selectedfrom the group consisting of dacron, silicone, polyurethane,polycarbonate, polyethylene, polyvinylchloride.
 21. A method ofinitiating a clotting cascade in a blood fluid and delivering the bloodfluid to a wound in a patient in order to close the wound, said methodcomprising the steps of: a) providing a clotting cascade initiationapparatus within which the blood fluid can be received, said apparatusincluding a substantially enclosed sterile containment chamber withinwhich the blood fluid can be received and retained; the containmentchamber containing a procoagulating agent within the substantiallyenclosed sterile containment chamber; wherein a clotting cascade can beinitiated when the blood fluid is placed into the sterile containmentchamber and exposed to the procoagulating agent; b) placing a sufficientamount of blood fluid into the containment chamber to provide asufficient amount of blood fluid to the wound, once the clotting cascadeis initiated, to enable the blood fluid to knit together to form a clot;and c) delivering the blood fluid to the wound subsequent to theinitiation of the clotting cascade in the containment chamber such thatthe clotting cascade can be completed and a clot can form within thewound.
 22. The method of initiating a clotting cascade of claim 21,wherein the procoagulating agent is a porous matrix and the step ofplacing the blood fluid in the chamber includes passing the blood fluidthrough the porous matrix.
 23. The method of initiating a clottingcascade of claim 21, wherein the procoagulating agent is biological inorigin
 24. The method of initiating a clotting cascade of claim 23,wherein the biologic material is a biologic material selected from thegroup consisting of cotton, diatomaceous earth.
 25. The method ofinitiating a clotting cascade of claim 21, wherein the procoagulatingagent is inorganic.
 26. The method of initiating a clotting cascade ofclaim 25, wherein the inorganic agent is glass.
 27. The method ofinitiating a clotting cascade of claim 21, wherein the procoagulatingagent is a synthetic polymer.
 28. The method of initiating a clottingcascade of claim 27, wherein the synthetic polymer is a syntheticpolymer selected from the group consisting of dacron, silicone,polyurethane, polycarbonate, polyethylene, polyvinylchloride.
 29. Amethod of initiating a clotting cascade in a blood fluid and deliveringthe blood fluid to a wound in a patient in order to close the wound,said method comprising the steps of: a) providing a clotting cascadeinitiation apparatus within which the blood fluid can be received and aclotting cascade can be initiated, said apparatus including asubstantially enclosed sterile containment chamber within which theblood fluid can be received and retained; b) placing a sufficient amountof blood fluid into the containment chamber to provide a sufficientamount of blood fluid to enable the blood fluid to knit together to forma clot once the clotting cascade is initiated; c) placing aprocoagulating agent within the substantially enclosed sterilecontainment chamber such that the procoagulating agent comes intocontact with the blood fluid and a clotting cascade is initiated inblood fluid; and d) delivering the blood fluid to the wound subsequentto the initiation of the clotting cascade in the containment chambersuch that the clotting cascade can be completed and a clot can formwithin the wound.
 30. The method of initiating a clotting cascade ofclaim 29, wherein the step of placing the procoagulating agent withinthe substantially enclosed sterile containment chamber includes placinga biocompatible procoagulating agent within the chamber such that theprocoagulating agent is mixed with the blood fluid.
 31. The method ofinitiating a clotting cascade of claim 30, wherein the biocompatibleprocoagulating agent is a biological material.
 32. The method ofinitiating a clotting cascade of claim 31, wherein the biologicalmaterial is a biocompatible procoagulating agent selected from the groupconsisting of thrombin, collagen, fibrin, fibrinogen.
 33. The method ofinitiating a clotting cascade of claim 30, wherein the biocompatibleprocoagulating agent is a synthetic compound.
 34. The method ofinitiating a clotting cascade of claim 33, wherein the syntheticbiocompatible procoagulating agent is aminocaproic acid.
 35. The methodof initiating a clotting cascade of claim 30, wherein the biocompatibleprocoagulating agent is an inorganic compound.
 36. The method ofinitiating a clotting cascade of claim 30, wherein the inorganicbiocompatible procoagulating agent is a salt.
 37. A method of initiatinga clotting cascade in a blood fluid and delivering the blood fluid to awound in a patient in order to close the wound, said method comprisingthe steps of: a) providing a clotting cascade initiation apparatuswithin which the blood fluid can be received and a clotting cascade canbe initiated, said apparatus including a substantially enclosed sterilecontainment chamber within which the blood fluid can be received andretained; b) placing a sufficient amount of blood fluid into thecontainment chamber to provide a sufficient amount of blood fluid toenable the blood fluid to knit together to form a clot once the clottingcascade is initiated; c) mechanically stressing the blood fluid withinthe substantially enclosed sterile containment chamber such that aclotting cascade is initiated in blood fluid; and d) delivering theblood fluid to the wound subsequent to the initiation of the clottingcascade in the containment chamber such that the clotting cascade can becompleted and a clot can form within the wound.
 38. The method ofinitiating a clotting cascade of claim 37, wherein the step ofmechanically stressing the blood fluid within the substantially enclosedsterile containment chamber is selected from the group consisting ofagitation, thermal induction.
 39. The method of claim 1; the additionalstep of applying direct pressure to an artery proximal to a wound in theartery thereby reducing arterial blood pressure while clot forms in thewound.
 40. The method of claim 11; the additional step of applyingdirect pressure to an artery proximal to a wound in the artery therebyreducing arterial blood pressure while clot forms in the wound.
 41. Themethod of claim 1; the additional blood fluid treatment with ananticoagulant inhibiting agent.
 42. The method of claim 41; theadditional blood fluid treatment with an anticlot inhibiting agent. 43.The method of claim 1; the additional blood fluid treatment with ananticlot inhibiting agent.
 44. The apparatus of claim 11; the additionalblood fluid treatment agent consisting of an anticoagulant inhibitingagent.
 45. The apparatus of claim 44; the additional blood fluidtreatment agent consisting of an anticlot inhibiting agent.
 46. Theapparatus of claim 11; the additional blood fluid treatment agentconsisting of an anticlot inhibiting agent.
 47. The apparatus of claim11; constituting a kit when combined with apparatus form the groupconsisting of: an introducer, guidewire, dilator, obturator, collapsiblecatheter sheath, Seldinger needle, balloon catheter, infusion catheter,stent, scalpel, suture line, needle, pouch, tray, tray lid, instructionsfor use, adhesive identification label, sterility indicator.